Oncology Drug Approval - Accelerated

Bridging the gap between biomarkers and In Vitro Companion Diagnostics

Sequencing and protein expression analyses provide complementary information about a tumor suppressor gene, which can be used to guide cancer treatment decisions.

Clinical Background:

Tumor suppressors such as LKB1, p53, and PTEN are central in regulating cellular fate and behavior. Loss of function in these tumor suppressors is common in the etiology of many cancers. Analysis of tumor suppressor function is especially challenging because a variety of genetic alterations (insertion, deletions, point mutations, promoter hyper-methylation, gene copy loss) may lead to tumor suppressor inactivation, yet not all genetic alterations affect protein expression and function.

Personalized cancer management for treating cancer patients with molecularly targeted therapy is still challenged by the following limitations:

Tumor heterogeneity – Tumors are heterogeneous and continuously evolving, complicating both the diagnosis and the assessment of acquired resistance. However, tumor biopsies are limited both spatially to the region biopsied and temporally based on the state of tumor evolution at the time of biopsy.2

MolecularMD NGS Data Analysis VIPR Pipeline

The advance in NGS technologies and the dramatic reduction in the cost of sequencing have fueled the utility of massive parallel sequencing in cancer research and clinical diagnosis. However, the complex and time consuming “post-sequencing” data analysis currently limits the clinical application of NGS.1 A data analysis pipeline is a combination of informatics tools used for processing the raw NGS sequence data, by aligning the raw reads and detecting variants. The data analysis pipeline established by a laboratory ultimately determines the types of variants that can be reliably called within the targeted genomic regions. Some pre-designed NGS cancer panels include a data analysis pipeline, but these rarely utilize the full range of tools that are available for NGS analysis. Other pre-designed NGS panels offer minimal analysis support. A poor-quality data analysis pipeline can substantially hinder the identification of clinically relevant mutations.